New discoveries open Pandora's Box of changing, predicting human behavior
by: Courtesy of Jorge Barraza Neuroeconomist Paul Zak, who says he always makes himself the first subject, is wired with EEG electrodes for an experiment to pinpoint parts of the brain involved in modulating trust.

Eran Klein, a neurologist at Oregon Health and Science University, is seeing more patients seeking Aricept, a memory-enhancing drug intended for people with Alzheimer's and other dementia diseases.

But many of Klein's patients aren't suffering from Alzheimer's or dementia. Some find that their memories aren't what they once were. Some have a family history of Alzheimer's and are wondering if they are in a pre-dementia state. Some just want to improve their memories.

And Klein, aware that there is little research on Aricept for disease-free people, has to decide who gets the prescription and who doesn't.

One thing Klein knows he can't do is count on public attitudes or medical guidelines to tell him what to do.

'As a society, we haven't decided whether or not we're going to condone medicines designed for enhancing certain features or characteristics of people,' he says.

On Monday, Feb. 27, OHSU hosts Henry Greely, director of the Stanford Law School Center for Law and Bioethics, as part of a series of speakers on Brain Awareness. On March 19, Alan Leshner, executive director of the American Association for the Advancement of Science, will speak about social and ethical issues resulting from advances in neuroscience.

Physicians like Klein, and neurological researchers around the country, say it's not just the future that has them worried. Recent advances in brain imaging have allowed scientists to pinpoint what substances affect areas of the brain, and which areas of the brain are responsible for specific thoughts and emotions. The result has been an opening of the floodgates for different types of brain enhancements.

Online companies are selling small bottles of aerosol spray they claim will encourage people to trust you. The amount of active ingredient in the bottles may be too diluted to do anything, but the hormone the bottles contian - Oxytocin - has been confirmed in clinical experiments to encourage trust.

Another drug, Propranolol, has been shown to have a side effect that blocks emotional memories. Administered before or after traumatic events - to soldiers entering battle and to women at hospital emergency departments immediately after sexual assaults - it may be able to prevent the brain from remembering the trauma.

It might keep both soldiers and assault victims from the lifelong torture of post-traumatic stress disorder.

But there are a number of people with a number of reasons for not embracing Propranolol's helpful side effects too quickly. They include lawyers and law enforcement officials who worry about the legal implications of the drug's use.

Ritalin and Adderol are commonly prescribed for attention deficit disorder. But a recent study showed that as many as one in four students at an Ivy League university were using one of the two not because they had a diagnosis, but because it helped them study.

'I've had several colleagues say to me, 'You're a stupid guy if you're not using Ritalin to stay up all night.' You're much more productive, your career takes off much faster,' says Paul Zak, director of the Center for Neuroeconomic Studies at Claremont Graduate University in California.

Zak isn't sure that those Ivy League students and his college professor colleagues are doing anything wrong.

'I'm very conflicted,' he says.

Retaining moral judgment

Zak's experiments were greatly responsible for the discovery of Oxytocin's trust effect on the brain. In fact, in his book 'The Moral Molecule,' Zak writes that Oxytocin, a hormone given to women to induce childbirth, can encourage people to feel more empathy for others and motivate them to be more connected to others. The 5 percent of the population that doesn't release Oxytocin on its own, he says, have many of the attributes of psychopaths.

Zak is well aware of the dangers of discoveries such as Oxytocin's effect. In 2005, he developed an Oxytocin inhaler and published his findings. Within three months, he began seeing liquid trust products for sale on the Internet.

'We open up the black box,' he says, adding that he suspects the Oxytocin in those products is too diluted to have any effect.

What worries Zak and others is that the black box is full of questions that nobody's taking time to answer. For example, Zak works with men in prison. Exhibitionists and flashers he has found particularly interesting because they have a high rate of recidivism - once out of prison they often expose themselves again. Jail time is little deterrence to them.

If Zak can treat them with a drug such as Oxytocin, keeping their urges suppressed, should he? What about jailed pedophiles? What about if the prisoners want the therapy? What if they don't?

Zak says ignoring these questions is a perilous choice.

'Like it or not, technology progresses, and we're going to have more of that information,' he says. 'Whether we know what to do with it is an open question. Do we want to be a society like 'Minority Report,' where we're drugging people before they've committed a crime? The answer is no, but it's a worry.'

Zak is intrigued by the implications of knowing the neurological causes behind criminal acts. He cites a Virginia case in which a man who had no criminal record molested his young stepdaughter around the same time he began compulsively viewing pornography. He was convicted and sentenced to jail for the abuse. In jail, he had a seizure. A subsequent brain scan showed he had a tumor pressing against an area of the brain responsible for producing dopamine, a chemical that affects behavior.

Surgeons removed the tumor and the man, in jail, lost his interest in pornography. Later, the tumor reappeared, along with the interest in pornography. The interest disappeared again when the second tumor was removed.

'We have a direct mapping now from (a) neurological disorder to a legal violation,' Zak says. 'Clearly this guy with a tumor is not his true self.'

Zak says his work with the U.S. military involves looking at ways to modify the neurological activity of soldiers. For example, he says, if soldiers prior to battle were given something to inhibit their natural release of Oxytocin, they could lose their inhibitions. That could make them fierce warriors. It could also, Zak says, dampen their ability to think morally, and increase the risk that they unnecessarily kill civilians.

No free lunch

Stanford's Greely says that brain enhancement might be getting the bulk of attention - a trust aerosol is a bit hard to resist - but using brain imaging to predict the future may be more contentious in the long run.

Greely would like to see a government approach to at least some of the new brain technology, something along the lines of the U.S. Food and Drug Administration, which approves new drugs before they can be released to market. Brain imaging lie detectors and pain detectors are two advances he'd put into that category.

Two U.S. companies sell MRI lie detection services. According to Greely, two U.S. cases have come to court where MRI lie detection was performed. But in both cases, judges ruled the results were inadmissible.

In 2008, a woman in India was found guilty of poisoning her ex-fiancé after a judge allowed a brain scan that ostensibly showed the woman had a memory of the crime, despite her own denials.

Greely doesn't believe brain imaging technology has been proven reliable enough yet for that to be allowed. But the U.S. firms that market their lie detection brain scans have patents on their technology and, he says, they aren't about to allow objective clinical trials to determine the accuracy of their work.

As for Propranolol, Greely anticipates a few cases where witnesses whose memories have been dulled, erased or changed by the drug will make it to court. Prosecutors might claim that providing a rape victim with the drug constitutes tampering with a witness, and that widespread use might make it impossible for them to send rapists to prison.

Judges will have to set precedents that legislators can use to decide if they want to get involved in making new laws, Greely says. But already, some hospital emergency departments in clinical trials are asking women brought to the hospital after sexual assaults if they want their memories dampened by Propranolol as a means of avoiding PTSD.

Erik Parens, a bioethicist at The Hastings Center in Garrison, N.Y., says Propranolol and variations that have yet to arrive constitute a double-edged sword.

'Nobody wants a drug that would erase all of our memories,' Parens says. 'Being a human being entails having memory. We do think that blunting memories for someone with PTSD is good. We have to get a grip on what kinds of memories we want to blunt.'

Parens is aware of marriage counselors who recommend that couples in therapy use Oxytocin to develop a more trusting environment. He's not certain that's a good idea. Not everybody, he says, is better off letting their defenses down.

Greely says brain imaging to determine whether someone is truly in pain is also on the way. That could be useful in hundreds of thousands of court cases, he notes. Car accident victims claiming whiplash might have to submit to brain imaging that could show whether they're telling the truth. Imaging could tell whether people applying for social security disability for back pain are deserving by looking at the areas of the brain that process pain.

Also not too far in the future are brain scans that will tell 60-year-olds if they are likely to develope Alzheimer's. They also could show parents which of their offspring will suffer from schizophrenia.

In both cases, Greely says, patients and physicians will have to decide the value of conducting the tests if there are no cures available, and if the tests are only, say, 90 percent certain.

OHSU's Klein says neurological enhancement also raises issues of fairness. Not everybody will have access to the drugs that make students smarter, for instance. On the other hand, much of that discussion isn't new.

'We take a lot of things that affect our behavior,' Klein says. 'We drink coffee, we exercise to get a hormone boost. We enhance ourselves and change our brain chemistry in all sorts of ways. The question is, is this somehow beyond accepted norms?'

Somebody needs to start answering those questions quickly, according to Greely. 'The research isn't stopping, it's accelerating,' he says. 'The knowledge is coming incredibly fast, and not enough people are thinking about this.'

Zak warns that norms are only half the equation. With new discoveries resulting from brain imaging seemingly arriving every month, both scientists and the public are forgetting that when it comes to technology, speed has its own drawback.

'There's no free lunch,' Zak says. 'There's always a tradeoff. Maybe that's the key point. Neurologically, we don't know the potential side effects, particularly in the long term.'

• Experiment tests belief in 'free will'

As scientists become more adept at decoding the brain and the signals that create our thoughts and emotions, some people will have their entire world views turned upside down.

New brain therapies appear to alter personalities. Some experiments are prompting scientists to question what we mean when we talk about free will.

'A neuroscientist might say there's no such thing as free will because we can measure what you're going to do before you do it,' says Paul Zak, director of the Center for Neuroeconomic Studies at Claremont Graduate University in California.

Zak is referring to variations on what is known as the Libet experiment. Scientists have been able to view a brain's image as a person is given a task such as pressing either a red or green button on a table. After a few presses, scientists have a map of which part of the brain becomes engaged when the person presses red and which is engaged for green. Then they are able to predict which button the person is going to press as much as 10 seconds before either of his hands have made a move, well before he is even conscious of making a decision.

Some say the experiment shows that physical action is preceded by complex patterns of thought or awareness. Others believe that the choice was never a matter of conscious free will, that what we believe to be decision making is actually intellectual rationalization after the fact.

Those who might have the most trouble with the decoding of the brain may be people who believe everything they do is controlled by a supreme being, says Eric Parens, a bioethicist at The Hastings Center in Garrison, N.Y.

'If you believe in a god that gave you a soul that is the seat of your decision making, then you will be shaken up by emerging neuroscience,' Parens says.

- Peter Korn

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